IMMUNOLOGY OF CHLAMYDIAL SURFACE ANTIGENS

这个项目的目标是开发一种亚单位疫苗

The goal of this project is the development of a subunit vaccine for the prevention of sexually transmitted diseases (STDs) caused by Chlamydial trachomatis. Towards this end our objectives are to: (i) identify and characterize antigenically common T-helper and neutralizing B-cell epitopes of the C. trachomatis major outer membrane protein, (ii) linkage of these key T-helper and B-cell protective epitopes as a chimeric peptide immunogen, (iii) evaluation of the immunogenic properties of the chimeric peptide, and (iv) targeting the chimeric peptide to evoke a sustained mucosal immune response. Antigenically common T-helper and B-cell epitopes of the MOMP were identified using recombinant DNA and peptide mapping methods. A synthetic oligopeptide corresponding to these epitopes was co-linearly synthesized and its immunogenic properties were studied in both mice and sub-primates. The chimeric T:B cell peptide was immunogenic in eight different strains of H-2 congenic B10 mice. Mouse anti-peptide antibodies bound to intact chlamydiae, and were capable of neutralizing the infectivity epidemiologically important C. trachomatis serovars in vitro. Sub-human primates were immunized with the peptide and their antibody responses were similarly studied. Primates immunized with peptide A8-VDIV produced high titer IgG antibodies that exhibited C. trachomatis species common neutralizing properties. The immunogenicity of peptide A8-VDIV in different strains of mice disparate at H-2, its immunogenicity in primates, and its ability to target neutralizing antibodies against multiple C. trachomatis serovars are encouraging in terms of the potential utility of the chimeric peptide immunogen as an experimental vaccine against chlamydial STDs. Future studies will focus on targeting the chimeric peptide to evoke mucosal immunity. This work will include incorporation of the peptide into biodegradable microspheres and the construction of E. coli heat labile toxin (LT) peptide fusions.